The intake and frequency of inhalation of volatile nitrites has been associated with the incidence of Kaposi's sarcoma in people suffering from AIDS. Animal and in vitro lymphocyte studies have shown that immune cell function can be altered by these agents. However, no study has related directly the effects of nitrites administered in vivo to disturbances of immune function in humans. Thus, a study has been conducted in healthy, HIV negative volunteers. An inhlation protocol in which the subject inhaled 3 doses of amyl nitrite for 3 days and 1 dose on the fourth day has been conducted. In an extended protocol a second group of volunteers were administered subsequent, single inhalations of nitrite 3-4 days apart, to a total of 13 inhalations over 3 weeks. A battery of immune function tests in the subjects' lyphocytes, was carried out on 2 occasions prior to the inhalation protocol, immediately following the last dose, and at 1, 4, and 7 days after the last dose. Results showed a decrease in natural killer cell activity, the lymphocyte function reputedly responsible for tumor cell scavenging. The single doses of nitrite administered at 3-4 day intervals continued to suppress this activity. Lymphocyte numbers and subsets were not altered during the inhalation protocols, but showed a non-specific rise on cessation of the drug. Discrepencies between mitogen stimulated [3H]thymidine incorporation, a measure of the activity potential of lymphocytes, and antibody production by the T lymphocyte-dependent, B-cells indicated a deficit in T-cell function during nitrite exposure. The nitrites were demonstrated to have minimal abuse potential.